2021
Renalase: A Multi-Functional Signaling Molecule with Roles in Gastrointestinal Disease
Pointer TC, Gorelick FS, Desir GV. Renalase: A Multi-Functional Signaling Molecule with Roles in Gastrointestinal Disease. Cells 2021, 10: 2006. PMID: 34440775, PMCID: PMC8391834, DOI: 10.3390/cells10082006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGastrointestinal DiseasesGastrointestinal TractHumansMonoamine OxidaseProtein IsoformsSignal TransductionConceptsProsurvival effectAcute cerulein pancreatitisRole of renalaseAnti-inflammatory effectsDisease modelsAcute organ injuryRelevant clinical settingsShortens life expectancyPreclinical disease modelsCell survivalHuman cancer tissuesCancer cell survivalOrgan injuryAcute injuryPancreatic cancerIntestinal diseaseGastrointestinal diseasesRodent modelsCerulein pancreatitisSelect cancersCancer tissuesRenalaseClinical settingTherapeutic agentsExport transporters
2017
Phosphorylated Presenilin 1 decreases β-amyloid by facilitating autophagosome–lysosome fusion
Bustos V, Pulina MV, Bispo A, Lam A, Flajolet M, Gorelick FS, Greengard P. Phosphorylated Presenilin 1 decreases β-amyloid by facilitating autophagosome–lysosome fusion. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 7148-7153. PMID: 28533369, PMCID: PMC5502640, DOI: 10.1073/pnas.1705240114.Peer-Reviewed Original Research
2016
Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer
Guo X, Hollander L, MacPherson D, Wang L, Velazquez H, Chang J, Safirstein R, Cha C, Gorelick F, Desir GV. Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer. Scientific Reports 2016, 6: 22996. PMID: 26972355, PMCID: PMC4789641, DOI: 10.1038/srep22996.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAntibodiesApoptosisCarcinoma, Pancreatic DuctalCell Cycle CheckpointsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryKaplan-Meier EstimateMaleMice, NudeMiddle AgedMonoamine OxidasePancreatic NeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionXenograft Model Antitumor AssaysConceptsRenalase expressionPancreatic cancerPancreatic ductal adenocarcinoma growthCohort of patientsPancreatic cancer tissuesPancreatic ductal adenocarcinomaPancreatic ductal adenocarcinoma cellsXenograft mouse modelAttractive therapeutic targetDuctal adenocarcinoma cellsTumor cell apoptosisOverall survivalPathogenic roleCell cycle arrestDuctal adenocarcinomaPrognostic makerTumor massMouse modelTherapeutic targetCellular injuryCancer tissuesRenalaseCancerAdenocarcinoma cellsGrowth factor
2014
Lactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity
Hoque R, Farooq A, Ghani A, Gorelick F, Mehal WZ. Lactate Reduces Liver and Pancreatic Injury in Toll-Like Receptor– and Inflammasome-Mediated Inflammation via GPR81-Mediated Suppression of Innate Immunity. Gastroenterology 2014, 146: 1763-1774. PMID: 24657625, PMCID: PMC4104305, DOI: 10.1053/j.gastro.2014.03.014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsArrestinsBeta-Arrestin 2Beta-ArrestinsCarrier ProteinsCell LineCeruletideChemical and Drug Induced Liver InjuryCytoprotectionDisease Models, AnimalDose-Response Relationship, DrugDown-RegulationGalactosamineHumansImmunity, InnateInflammasomesInjections, IntraperitonealInterleukin-1betaLipopolysaccharidesLiverMacrophagesMaleMiceMice, Inbred C57BLMonocytesNF-kappa BNLR Family, Pyrin Domain-Containing 3 ProteinPancreasPancreatitisReceptors, G-Protein-CoupledRNA InterferenceRNA, Small InterferingSignal TransductionSodium LactateToll-Like Receptor 4Toll-Like ReceptorsTransfectionConceptsToll-like receptorsRelease of IL1βAdministration of lipopolysaccharideOrgan injuryNF-κBCaspase-1TLR inductionAcute pancreatitisPyrin domain-containing protein 3Administration of lactatePromising immunomodulatory therapyAcute liver injuryAcute organ injuryMacrophages of miceDomain-containing protein 3Production of IL1βRAW 264.7 cellsConcentration of lactateAcute hepatitisImmunomodulatory therapyImmune hepatitisPancreatic injuryLactate receptorLiver injuryNLRP3 inflammasomeAdenylyl cyclases in the digestive system
Sabbatini ME, Gorelick F, Glaser S. Adenylyl cyclases in the digestive system. Cellular Signalling 2014, 26: 1173-1181. PMID: 24521753, PMCID: PMC4441802, DOI: 10.1016/j.cellsig.2014.01.033.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsCatalytic DomainDigestive SystemDigestive System Physiological PhenomenaHumansIsoenzymesPancreatitisSignal Transduction
2012
Sterile Inflammatory Response in Acute Pancreatitis
Hoque R, Malik AF, Gorelick F, Mehal WZ. Sterile Inflammatory Response in Acute Pancreatitis. Pancreas 2012, 41: 353-357. PMID: 22415665, PMCID: PMC3306133, DOI: 10.1097/mpa.0b013e3182321500.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsHumansInflammationInflammation MediatorsPancreasPancreatitisSignal TransductionConceptsDamage-associated molecular patternsSterile inflammatory responseAcute pancreatitisInterleukin-1βInflammatory responseExperimental pancreatitisNOD-like receptor protein 3High mobility group box protein 1Toll-like receptor 4Remote organ injuryReceptor protein 3Acinar cellsExperimental acute pancreatitisIL-1 receptorNovel therapeutic targetBox protein 1Necrotic acinar cellsDAMP receptorsShock protein 70Disease resolutionPancreatic injuryOrgan injuryInitial injuryIL-18Pharmacologic antagonism
2011
TLR9 and the NLRP3 Inflammasome Link Acinar Cell Death With Inflammation in Acute Pancreatitis
Hoque R, Sohail M, Malik A, Sarwar S, Luo Y, Shah A, Barrat F, Flavell R, Gorelick F, Husain S, Mehal W. TLR9 and the NLRP3 Inflammasome Link Acinar Cell Death With Inflammation in Acute Pancreatitis. Gastroenterology 2011, 141: 358-369. PMID: 21439959, PMCID: PMC3129497, DOI: 10.1053/j.gastro.2011.03.041.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAnimalsAnti-Inflammatory AgentsApoptosisApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1CeruletideCytoskeletal ProteinsDisease Models, AnimalDNAInflammasomesInterleukin-1MacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutNecrosisNeutrophil InfiltrationNLR Family, Pyrin Domain-Containing 3 ProteinPancreasPancreatitisPneumoniaProtein PrecursorsPurinergic P2X Receptor AntagonistsReceptors, Purinergic P2X7RNA, MessengerSeverity of Illness IndexSignal TransductionTaurolithocholic AcidToll-Like Receptor 9ConceptsToll-like receptor 9Acute pancreatitisWild-type miceAcinar cell deathPancreatic edemaTaurolithocholic acidDamage-associated molecular pattern receptorsResident immune cellsCell deathImmune cell populationsDevelopment of inflammationInitiation of inflammationCell populationsNew therapeutic strategiesMolecular pattern receptorsDAMP receptorsLung inflammationInflammatory infiltrateTLR9 expressionImmune cellsPancreatic necrosisReceptor 9TLR9 antagonistInflammasome activationPurinergic receptors
2009
The Acinar Cell and Early Pancreatitis Responses
Gorelick FS, Thrower E. The Acinar Cell and Early Pancreatitis Responses. Clinical Gastroenterology And Hepatology 2009, 7: s10-s14. PMID: 19896090, PMCID: PMC3073378, DOI: 10.1016/j.cgh.2009.07.036.Peer-Reviewed Original ResearchConceptsAcinar cellsAcid loadForms of pancreatitisAcute acid loadSpecific calcium channelsInhibition of secretionPathologic responseAcute pancreatitisPancreatic acinar cellsPathological elevationAbnormal calciumPancreatitis eventsCalcium-dependent phosphataseAlcohol abuseCalcium channelsHarmful stimuliSmall intestineCalcium releasePancreatitisTrypsinogen activationPancreatitis responsesCalcium occursSpecific intracellular signalsActivationIntracellular signals
2008
Protein kinase C in the pancreatic acinar cell
Gorelick F, Pandol S, Thrower E. Protein kinase C in the pancreatic acinar cell. Journal Of Gastroenterology And Hepatology 2008, 23: s37-s41. PMID: 18336661, DOI: 10.1111/j.1440-1746.2007.05282.x.Peer-Reviewed Original ResearchConceptsProtein kinase CKinase CCell-free reconstitution systemPancreatic acinar cellsAcinar cellsPathological responseSpecific PKC isoformsPathogenesis of pancreatitisReconstitution systemCellular eventsPKC isoformsActivation of proteasesApical secretionProtease activationCell eventsInflammatory mediatorsAcute pancreatitisPathological activationSupraphysiological concentrationsPancreatitisPathological effectsPancreatic aciniCholecystokininCellsActivation
1995
Ca2+/calmodulin-dependent protein kinase II activation and regulation of adrenal glomerulosa Ca2+ signaling
Fern RJ, Hahm MS, Lu HK, Liu LP, Gorelick FS, Barrett PQ. Ca2+/calmodulin-dependent protein kinase II activation and regulation of adrenal glomerulosa Ca2+ signaling. American Journal Of Physiology 1995, 269: f751-f760. PMID: 8594869, DOI: 10.1152/ajprenal.1995.269.6.f751.Peer-Reviewed Original ResearchConceptsCaMKII activityBovine adrenal glomerulosa cellsDepolarization-induced increaseAdrenal glomerulosa cellsDepolarization-induced Ca2Voltage-gated Ca2Independent CaMKII activityElevated extracellular potassiumDependent protein kinase II (CaMKII) activationCaMKII inhibitor peptideAgonist-induced stimulationAldosterone secretagoguesAngiotensin IIGlomerulosa cellsKinase activityExtracellular potassiumImportance of CaMKIIIntracellular Ca2Dependent protein kinase IIProtein kinase IICell treatmentKN-62Calmodulin antagonistsCell-permeable inhibitorChannel activityCalmodulin-dependent protein kinases in rat glioblastoma.
Cheng EH, Gorelick FS, Czernik AJ, Bagaglio DM, Hait WN. Calmodulin-dependent protein kinases in rat glioblastoma. Molecular Cancer Research 1995, 6: 615-21. PMID: 7647041.Peer-Reviewed Original ResearchConceptsCaM-dependent protein kinaseProtein kinaseKinase II activitySignal transductionCaM kinase II activityKinase IICalmodulin-dependent protein kinaseCalcium-dependent signal transductionCaM-dependent protein kinase IIExogenous synapsin ICell cycle regulationII activityCaM kinase IIIElongation factor 2Protein kinase IICell linesCaM kinase IINumerous malignant cell linesSpecific peptide substratePhosphopeptide mappingKinase IIIAbnormal cell growthCycle regulationKinase activityKinase
1994
Cell cycle-dependent and kinase-specific regulation of the apical Na/H exchanger and the Na,K-ATPase in the kidney cell line LLC-PK1 by calcitonin.
Chakraborty M, Chatterjee D, Gorelick FS, Baron R. Cell cycle-dependent and kinase-specific regulation of the apical Na/H exchanger and the Na,K-ATPase in the kidney cell line LLC-PK1 by calcitonin. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 2115-2119. PMID: 8134357, PMCID: PMC43320, DOI: 10.1073/pnas.91.6.2115.Peer-Reviewed Original ResearchConceptsNa/H exchangerApical Na/H exchangerH exchangerAmiloride-sensitive 22Na uptakeCell line LLC-PK1Potent natriuretic effectKidney tubulesNa transport systemLLC-PK1K-ATPaseCa/calmodulin-dependent protein kinase IINatriuretic effectSerum calciumCalmodulin-dependent protein kinase IIProximal kidney tubuleCalcitoninCell cycle-specific activationProtein kinase IIReabsorptionTubulesSame cellsKinase IICellsApical exchangerS phase